We plan to continue to probe the mechanisms by which morphine, enkephalins, and beta-endorphins specifically inhibit the synthesis of cell surface sialoglycosphingolipids and glycoproteins in neuroblastoma expressing opiate receptors. Particular emphasis will be placed on a hypothesis that certain glycosyltransferases are activated by phosphorylation involving a hormone-sensitive adenylate cyclase-protein kinase system and that this adenylate cyclase is inactivated when opiates and opiate peptides occupy the appropriate ligand binding site. We believe that our model can explain the pharmacological changes observed in tissues of opiate-addicted animals, and we will continue studies on the cellular effects of chronic opiate and opioid peptide exposure by determining ion fluxes in naive, acute and chronically exposed cells and relating any flux changes to changes in cell surface negative charge. We will further investigate the mechanism of corticosteroid induction of myelin-associated enzymes (sulfotransferase and 2,3-cyclic nucleotide phosphohydrolase) in oligodendroglioma cell lines and bulk-isolated lamb oligodendrocytes. Particular emphasis will be placed on the role of cyclic AMP as a potentiator of the induction and the use of Brd Urd to block expression of differentiated products. Comparative biochemistry of two human alpha-fucosidases will be carried out with respect to structure, receptor-mediated high affinity uptake (using (125I)-labelled ligands and a range of inhibitors which should shed light on the nature of the receptor and the recognition site on the enzyme) and substrate specificity. We hope that these studies will lead to more efficient enzyme replacement therapy in patients with inherited mental retardation syndromes.